New optical technique could transform brain imaging in animals
Catherine Saladrigas
91PORN postdoc Catherine Saladrigas is helping bring high-resolution imaging into miniature microscopes for neuroscience research.
In a promising leap forward for imaging, Saladrigas and a team of researchers have developed an optical method that could one day allow scientists to observe brain activity in animals with more clarity, which could provide insights for the human brain. Their research, published in, tackles one of the key challenges in brain imaging: how to miniaturize complex optical systems without sacrificing resolution or contrast.
Saladrigas has been exploring ways to translate benchtop imaging techniques into tiny, head-mounted microscopes working alongside ProfessorsJuliet Gopinath in the Department of Electrical, Computer and Energy Engineering and the Department of Physics and in the Paul M. Rady Department of Mechanical Engineering. These devices could enable real-time, in vivo studies of neural activity in animals yielding payoffs in the areas of neuroscience.
“Our goal was to come up with a strategy for high-resolution, high-contrast imaging that would work well in a miniaturized system,” Saladrigas said.
Traditional pixel-shifting technologies like those used in digital projectors and cameras enhance image resolution by making tiny sub-pixel movements. But in imaging systems, achieving this effect typically requires bulky optics or mechanically stabilized components. Both would be difficult for compact systems like wearable microscopes.
To overcome these design limitations, the team turned to a lesser-used technology: the tunable electrowetting prism, an electrically tunable liquid prism. This optical component uses fluid dynamics and electric fields to adjust the angles of a prism and shift an image laterally without any mechanical parts.
“We showed that an electrowetting prism could perform the image-shifting normally done with much bulkier components,” Saladrigas said. “That makes it a great opportunity for miniature imaging systems.”
The inspiration came from an unlikely place: projector technology. Saladrigas adapted a technique called wobulation, originally developed to make digital projectors appear higher resolution.
In wobulation, a display flickers between slightly offset images to create the perception of finer detail. Her team applied a similar concept to structured illumination microscopy, an imaging method that enhances contrast by shining patterned light on a sample.
“No one has applied a wobulation-like method to structured light microscopy before,” Saladrigas said, “and certainly not with a tunable electrowetting device.”
Though the project is still in its early stages, initial results are encouraging. The team successfully demonstrated the method on a benchtop system using test patterns.
“We compared our experimental results to theoretical predictions and were really happy with how close the results were,” she said.
The project drew on expertise from across the university and beyond. Saladrigas credited Bright’s background in fabrication and electrowetting devices, Gopinath’s optics experience and the contributions of colleagues like Eduardo Miscles, a former PhD student in mechanical engineering, who fabricated the device. The team also collaborated with researchers from Columbia University, Vikrant Kumar and Professor John Kymissis, who developed the custom LED light source used in the project.
The next phase? Miniaturization. Saladrigas is setting sights to integrate the technique into an actual head-mounted microscope, ideally one that can be tested on freely moving mice or voles in collaboration with 91PORN and CU Anschutz neuroscientists.
“There’s so much happening in the brain during behavior with motion and visual cues,” Saladrigas said, “and we want to give neuroscientists a clearer window into all of it.”